title: Structure and proposed activity of a member of the VapBC family of toxin-antitoxin systems. VapBC-5 from Mycobacterium tuberculosis.
abstract: In prokaryotes, cognate toxin-antitoxin pairs have long been known, but no three-dimensional structure has been available for any given complex from Mycobacterium tuberculosis. Here we report the crystal structure and activity of a member of the VapBC family of complexes from M. tuberculosis. The toxin VapC-5 is a compact, 150 residues, two domain alpha/beta protein. Bent around the toxin is the VapB-5 antitoxin, a 33-residue alpha-helix. Assays suggest that the toxin is an Mg-enabled endoribonuclease, inhibited by the antitoxin. The lack of DNase activity is consistent with earlier suggestions that the complex represses its own operon. Furthermore, analysis of the interactions in the binding of the antitoxin to the toxin suggest that exquisite control is required to protect the bacteria cell from toxic VapC-5.
authors.affiliation: UCLA-DOE Institute of Genomics and Proteomics, the Department of Biological Chemistry, David Geffen School of Medicine, Molecular Cell and Developmental Biology, and the Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California 90095-1570.
authors.forename: Linda
authors.initials: L
authors.lastname: Miallau
authors.affiliation: UCLA-DOE Institute of Genomics and Proteomics, the Department of Biological Chemistry, David Geffen School of Medicine, Molecular Cell and Developmental Biology, and the Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California 90095-1570.
authors.forename: Michael
authors.initials: M
authors.lastname: Faller
authors.affiliation: UCLA-DOE Institute of Genomics and Proteomics, the Department of Biological Chemistry, David Geffen School of Medicine, Molecular Cell and Developmental Biology, and the Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California 90095-1570.
authors.forename: Janet
authors.initials: J
authors.lastname: Chiang
authors.affiliation: UCLA-DOE Institute of Genomics and Proteomics, the Department of Biological Chemistry, David Geffen School of Medicine, Molecular Cell and Developmental Biology, and the Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California 90095-1570.
authors.forename: Mark
authors.initials: M
authors.lastname: Arbing
authors.affiliation: UCLA-DOE Institute of Genomics and Proteomics, the Department of Biological Chemistry, David Geffen School of Medicine, Molecular Cell and Developmental Biology, and the Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California 90095-1570.
authors.forename: Feng
authors.initials: F
authors.lastname: Guo
authors.affiliation: UCLA-DOE Institute of Genomics and Proteomics, the Department of Biological Chemistry, David Geffen School of Medicine, Molecular Cell and Developmental Biology, and the Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California 90095-1570; UCLA-DOE Institute of Genomics and Proteomics, the Department of Biological Chemistry, David Geffen School of Medicine, Molecular Cell and Developmental Biology, and the Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California 90095-1570; UCLA-DOE Institute of Genomics and Proteomics, the Department of Biological Chemistry, David Geffen School of Medicine, Molecular Cell and Developmental Biology, and the Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California 90095-1570.
authors.forename: Duilio
authors.initials: D
authors.lastname: Cascio
authors.affiliation: UCLA-DOE Institute of Genomics and Proteomics, the Department of Biological Chemistry, David Geffen School of Medicine, Molecular Cell and Developmental Biology, and the Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California 90095-1570; UCLA-DOE Institute of Genomics and Proteomics, the Department of Biological Chemistry, David Geffen School of Medicine, Molecular Cell and Developmental Biology, and the Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California 90095-1570; UCLA-DOE Institute of Genomics and Proteomics, the Department of Biological Chemistry, David Geffen School of Medicine, Molecular Cell and Developmental Biology, and the Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California 90095-1570. Electronic address: david@mbi.ucla.edu.
authors.forename: David
authors.initials: D
authors.lastname: Eisenberg
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020836:Protein Structure, Quaternary / Q000502:physiology; D017433:Protein Structure, Secondary / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D008562:Membrane Glycoproteins; C077517:VapB protein, Bacteria